The proposed R03 pilot study will combine two traditional gene delivery vectors into a novel hybrid device with potential to surpass the gene delivery efficacy of either original vector. Biomaterials have been a primary vehicle to facilitate gene delivery due to their inherent biocompatibility and adjustable properties available to influence cellular delivery mechanisms. More recently, bacterial vectors have also been used for gene delivery and provide an orthogonal set of biological engineering parameters to further influence the cellular gene delivery process. In this work, a hybrid biomaterial-bacterial device will be generated that combines the best features of both individual vectors. More specifically, previous studies using either biomaterial or bacterial vectors for targeted antigen presenting cell gene delivery will now be combined in an effort to boost gene delivery efficacy to these particular cells. Improved gene delivery as a result of the new hybrid biomaterial- biological vectors will establish the technology as innovative. More importantly, the hybrid devices will provide a completely new platform for engineering design that includes disparate tools such as polymer chemistry and molecular biology to further modify and technically advance the potency of the vectors. This will be a key theme of future grant submissions as will be the application of the new devices, facilitated through established connections between Tufts'Schools of Engineering and Medicine, as genetic vaccines against infectious disease and cancer. PUBLIC HEALTH RELEVANCE: Success will provide two health-related outcomes: 1) a completely new gene delivery device with biological and biomaterial engineering tools available for future optimization and 2) a broad platform technology to be dedicated to new disease models and more advanced therapeutic applications.